Humans never truly dine alone. Our gastrointestinal tracts harbor complex microbial communities (the gut microbiota) that encode a vast array of enzymatic activities, contributing to the metabolism of our diet and the drugs we take. Research over the past decade has emphasized that our microbial co-conspirators are not just passive bystanders – they are a key factor that shapes our health and predisposition to disease. Yet the molecular mechanisms responsible often remain unknown, making it challenging to translate these findings to new therapies and diagnostics, or to appreciate the broader biological, ecological, and evolutionary implications. As a tractable first step, members of the Turnbaugh lab have chosen to focus on the microbial metabolism of and resistance to xenobiotics, including host-targeted drugs, antibiotics, and diet-derived bioactive compounds. These compounds are ideal for study due to their biochemical novelty and well-documented effects on human and rodent physiology. Furthermore, gut microbes are known to influence the efficacy and toxicity of >40 xenobiotics through both direct and indirect interactions. To study these complex microbial ecosystems, we use a combination of metagenomic sequencing, single cell analyses such as flow cytometry, and gnotobiotic mice (from the Greek roots gnostos 'known' and bios 'life'). Our major goals are to: (i) elucidate the bacterial taxa and metabolic pathways responsible for xenobiotic metabolism; (ii) determine how microbial communities adapt during exposure to xenobiotics; and (iii) test the relative importance of host, microbial, and environmental factors in determining drug bioavailability, efficacy, and toxicity using gnotobiotic mice. Ultimately, we aim to obtain a more comprehensive view of metabolism, yielding fundamental insights into host-microbial interactions, and supporting translational efforts to predict and/or manipulate the metabolic activities of our resident gut microbes.